We propose to continue our studies of a) exocrine gland physiology and b) exocrine gland dysfunction in cystic fibrosis. Our work on exocrine gland physiology will be directed towards obtaining fundamental, direct information in the following areas: 1) Cellular secretory mechanisms for ions and macromolecules in exocrine glands of experimental animals; 2) Same cellular secretory mechanisms in the human parotid gland; 3) Transacinar secretory mechanisms for secretion of electrolytes and water in exocrine glands; 4) Transductal fluxes and "secretion-transductal fluxes coupling" for ions and water in exocrine glands. We hope to improve knowledge of exocrine gland physiology and in this way contribute to the ultimate solution to cystic fibrosis as well as to other problems of human exocrine gland dysfunction in disease. In cystic fibrosis, we plan to complete our in vitro investigation of the electrolyte abnormality of exocrine glands (microperfusion of sweat, parotid and pancreatic ducts), study the cellular pathophysiology of enzymatically dispersed, functionally intact acinar cells from the parotids of patients obtained immediately after death, evaluate the possible pathogenetic relationship between polyamine metabolism and cystic fibrosis and develop an in vitro assay system for the detection of homozygotes from heterozygotes prenatally as well as antenatally and for the search for the molecular defect of the disease.